Figure 12.

VPA promotes the generation of Treg cells. Naïve T lymphocytes that are treated with VPA differentiate into Treg cells due to epigenetic modifications (H4 histone acetylation) that allow the entry of the transcription factors Ets-1, Ets-2, and PU.1 into the promotor region of Foxp3, which induces its transcription and translation. VPA also increases the expression of miRNA-21, miRNA-18c, and miRNA-327, as well as of CD25, which are characteristic of Treg lymphocytes. However, it also induces the exhaustion molecule CTLA-4. Interestingly, VPA-induced Treg cells can block the proliferation of PBMC and T effector lymphocytes. Green arrows indicate the processes, molecules, or mediators in the signaling pathway that are augmented and/or promoted by VPA. Red arrows indicate processes, molecules, or mediators in the signaling pathway that are inhibited by VPA.